At 42:45 Dr. Bob Melamede explains the neuronal influence of endocannabinoids. Start with the idea that any energy usage in the body, as in the activation of neurotransmitters, and the opening and functioning of calcium channels, is change and creates free radicals. It's the creation of these dangerous molecules, a natural and necessary part of the flow of energy maintenance in the system, that cues the ECS to create endocannabinoids.

Everything vibrates. It must be the tone of the vibration of the free radicals setting off some sort of mechanism that creates the cannabinoids.

We are so wonderfully made.

:laugh2: At 1:11 he justifies my belief that conservatives are likely not to have been breastfed as infants.

At 1:12 it becomes a discussion on how political leanings are a result of ECS breakdown in the brain, likely a lack of either receptors or an inability to create adequate cannabinoids to protect the body from stress. I'd think it'd more likely be lack of receptors. That's just a guess on my part.

***Let me know if this link isn't allowed. I'm not sure of the linking rules yet.***

Rendering of the 3D architecture of cytofilament bundles (in gold) tunneling through a cell's nucleus. The nuclear membrane is shown in blue.
Credit: Manfred Auer/Berkeley Lab
It is said that a picture is worth a thousand words, but new images of structural fibers inside a cell may represent more than a million words from hundreds of research papers spanning the past three decades.

The images, obtained by scientists at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab), show thread-like cytofilaments reaching into and traversing a human breast cell's chromatin-packed nucleus. It provides the first visual evidence of a physical link by which genes can receive mechanical cues from its microenvironment.

The images appear in a study featured on the cover of the Journal of Cell Science in a special issue on 3D Cell Biology published this month. The work leading up to the images began in the early 1980s when Berkeley Lab's Mina Bissell proposed the idea that gene expression and cell fate were dependent on their physical surroundings called extracellular matrix.

"There are somewhere between 30-70 trillion cells in our bodies, all with the same DNA sequence, so I've been saying since 1981 that something other than the sequence of the genes had to allow a nose to be a nose and not an elbow," said Bissell, Distinguished Scientist at Berkeley Lab's Biological Systems and Engineering Division and co-corresponding author of this study. "When the shape changes, biology changes."

The concept that phenotype is dominant over genotype was initially met with great skepticism, but it has since become accepted in the field. Before this, it was believed that the dominant signals dictating cellular function and form were controlled only by soluble small molecules such as hormones and growth factors, whereas extracellular matrix (ECM) molecules outside the cells were large insoluble proteins.

Evidence builds for mechanical influence

Hundreds of papers, including some 400 led by or co-authored by Bissell, have since provided critical clues showing that signals from physical forces outside a cell could dramatically alter a cell's function. By growing cells in a 3-D gel that includes extracellular matrix, researchers coaxed samples of breast cells from lactating mice to produce milk. This showed that cell function depended on having the proper 3-D growth environment.

"We knew the extracellular matrix was affecting gene expression, but it wasn't understood until now that the cytoskeleton was actually able to connect inside the nucleus," said Bissell. "Now we know there's a direct connection to the nucleus. That's what we're showing here for the first time. This is absolutely novel."

Bissell teamed up with Manfred Auer, head of the Cell and Tissue Imaging Department at Berkeley Lab's Molecular Biophysics and Integrative Bioimaging Division and co-corresponding author of the study.

"It took advances in cryogenic sample preparation techniques and large-volume electron microscopy to come up with these images," said Auer.

"We combined a record-breaking six different imaging techniques and hundreds of millions of data points to obtain these images," said Auer. "The integrative bioimaging approach involved three different optical light and three different electron microscopy imaging approaches, each with its own strengths. This new integration of imaging approaches is what allowed us to study something as complex as this cytofilaments system."

With the clarity provided by the super-resolution imaging, the researchers could show that the cytoskeleton coalesced with SUN proteins, a type of protein involved in connections between the donut-shaped nucleus and cell cytoplasm.

"This study establishes for the first time the long-postulated mechanical link between the cell's nucleus to adhesion complexes that allow communication with the surrounding extracellular matrix and other cells," said Auer.

What had been previously seen through other imaging techniques were telltale cytoskeletal tracks going through the cytoplasm of the cell, but it took this high-powered integrated bioimaging used in the study to reveal deep invaginations into and through the cell nucleus. The invaginations contained cytofilaments anchored at the nuclear membrane, thus providing a macromolecular highway allowing cables of cytofibers, which are known to interact with the extracellular matrix, to travel from the outside of the cell to its nucleus.

"The reason we're excited is that it explains a whole lot of literature of how force and tension could be playing a role together with biochemical signals to bring about huge changes in a cell," said Bissell.

Story Source:

Materials provided by Lawrence Berkeley National Laboratory. Note: Content may be edited for style and length.

* CB1
- central nervous system (brain and spinal cord)
- in cases of brain injury CB2 receptors will arise spontaneously in the brain to get to work reducing inflammation
- the most abundant cannabinoid receptor. Makes sense, considering the number of brain cells in the average human.
- thought to effect memory and adverse memories (think PTSD), appetite, response to rewards, our propensity to addiction, how we deal with stress, how we experience pain and how that can be managed.
- These are big quality of life issues. Create balance and you improve the patient's life, and enhance the journey to homeostasis.

* GPR55
- generating excitement in cancer treatment
- Different cancers respond to different cannabinoids in different ways. Some respond well to THC and don't respond well to CBD. In some cases CBD seems to be the wisest choice. We need more studies.
- When GPR55 is active it promotes tumor cell proliferation. More cancer cells are being made.
- It's believed that CBD can inhibit the activity of this receptor.
- Researches are looking into whether this pathway can be used to treat gliomas

* VR1 Vanilloid receptor
- Has a role in our perception of pain, the regulation of body temperature, inflammation, and may be why CBD works as a pain medication for neuropathy.
- Plays a role in sexual arosal, and has a dose-dependent response.
- At high doses other parts of the receptor are activated, which explains why some benefits of cannabis are dose-dependant. The receptors sometimes react differently to lower doses than higher doses. More isn't necessarily better. Find the sweet spot for you.

* 5HT Seratonin receptor
- the same one that SSRI drugs target (Wellbutrin, Prozac, Lexapro, etc)
- CBD can be a safe alternative to these drugs, without the significant side effects they present.
- SSTIs interrupt REM sleep. Disrupt it for years and you end up with things like fibromyalgia, IBS, anxiety, etc.
- Sometimes when these drugs stop working they can create anxiety response.
- CBD has anti-anxiety properties
- The receptor is also involved in addiction,appetite, sleep, pain, nausea, and vomiting.
- An important receptor to keep in balance. Witness the number of humans on anti-anxiety drugs.

The reasons cannabinoids offer the relief they due is based on biochemistry and the architecture of the ECS

Alpha helix proteins form the receptors. They pass through the cell membrane to form a link to the interior. Below the receptor is a G-protein sub unit. When a neurotransmitter drops into the receptor it changes the shape of the receptor. This change causes a corresponding change in the shape of the G-protein that initiates a chemical event that creates a new sub unit that goes on to become a neurotransmitter. This new neurotransmitter then goes on to activate another receptor, starting the sequence all over again and extending the reach of the neurotransmitters. The resultant sequence of new neurotransmitters being created is called a cascade event. A cascade of signal events.

This is the way all neurotransmitters work in your body.

More receptors are being discovered all the time.

CBD can act as a regulatory molecule as well as the main receptor activator.
- There are auxiliary attachments on the cell and CBD can activate them, changing the affinity of that receptor for that molecule. and thereby the function of the CB receptor.
- CBD can interact with the CB1 receptors and down-regulate the sensitivity of the receptor. This is how CBD modifies the euphoric experience of THC.

Metabolism of cannabinoids

Enzymes essentially do a shape change of the cannabinoids by binding to the molecule and then splitting the components apart for elimination from the system.
- Sometimes there will be a sugar molecule added to hasten elimination
- Most cannabinoids (about 80%) are excreted in feces.
- Your urine is what's tested because the labs don't want to be testing feces. Heavy users can hold onto detectable cannabinoids for up to 80 days.
- Cannabinoids hide out in fat cells. If you have excess fat you have a plethora of binding spots.

There are receptors in placenta tissue. Cannabinoids are found in breast milk. Just worth knowing. No studies have linked cannabinoids in an infant that caused detrimental effects. Consider the potential effects and make your own decisions.

Basics:
- Cannabis sativa makes trichomes, which are filled with the essential oil of the plant. This oil includes cannabinoids and terpenoids.
- Cannabinoids bind to the CB receptors found in the body. Most are CB1, and are found in the brain.
- The receptors are like the locks, and cannabinoids are the keys that unlock the receptors.
- Endogenous cannabinoids (anandamide and 2-AG, surely among others, yet to be identified) are those produced by your own body.
- They're created on site and on demand, and bind to the CB1 receptor.
- There are 3 kinds of cannabinoids,
1) phytocannabinoids: basically, 21-carbon items from cannabis, with exception of plants that have Beta-Caryophyllene, which activates the CB2 receptors
2) endocannabinoids: produced by the body
- The ECS has been described as having functions regulating Relaxation Appetite, Sleep, Memory (I always forget this one :laugh2:), and Protection. Rest, Eat, Sleep, Forget, Protect
3) synthetic cannabinoids: some developed before we knew about receptors, some after
- In the brain endogenous cannabinoids act in a retrograde fashion, downregulating the neurotransmitters, originating in the post-synaptic neuron and traveling upstream to attach to CB1 receptors on the other side of the gap. The primary reason for their attachment is to reduce the release of neurotransmitters.
- They're damping down whatever particular function and response that neuron is set for.
- Found throughout the animal kingdom in cordates, animals with a spinal cord

From Medical Jane (highlights are mine): Specialized receptors are located throughout the human body, including but not limited to, in the hippocampus, (memory and learning), the cerebral cortex ( decision making, emotional behavior), the cerebellum (motor control, coordination), putamen (movement, learning), the hypothalamus (appetite, body temperature), and the amygdala (emotions).

When a specific cannabinoid or a combination of cannabinoids bind to a specialized receptor, an event or a series of events, is triggered in the cell, resulting in a change in
- the cell's activity
- its gene regulation and/or the signals that it sends to neighboring cells through the process we call "signal transduction."

3. enzymes that make cannabinoids and break them down; these can be be manipulated pharmacologically and serve as medicines as well

Entourage Effect
- You have anandamide and 2-AG, but there're also other compounds within the body that, on their own, don't have much power, but working synergistically can deliver a powerful therapeutic punch.
- Soloists and supporting cast.

CB1 receptors in the brain are located heavily in areas that're nociceptive, places having to do with mediating pain
- Additionally found the cerebellum, the limbic system, (emotion), the basal ganglia (movement)
- Receptors are also in reward pathways (addiction and its many effects on the system)
- Receptors aren't found in the areas of the brain having to do with respiration, so cannabinoids can't kill you like all the wonder drugs can. This is how opioids kill. :17: They depress the respiratory center of the brain and your body forgets to breathe.

The cannabinoids also work in the spinal cord, in the periphery, and in the gut.
- CB1 is the most prolific CB G-protein receptor in the brain, where it modulates the release of neurotransmitters.
- Glutamate is typically overactive in neuropathic pain. If cannabinoids damp down glutamate response, that would effect pain over time.
- Modulates pain, memory, movement, whether someone will vomit or not, their seizure threshold.
- Also modulate many other body systems, incl. the gut.

The brain and the gut speak for themselves same language.
- Cannabinoids mo
- propulsion: the speed with which things move through the gut
- secretion: how much liquid or lack of liquid is brought into play during digestion and elimination
- One of the first successful treatments for cholera (major symptom is deadly diarrhea) in the 19th century was cannabis.

If we think of CB1 as the psychoactive receptor we then look at CB2 receptors, found mainly in the periphery, as pain and inflammation.
- Drugs that could effect only CB2 receptors wouldn't have any euphoric effect.
- Such drugs could be promising in treating fibrotic diseases like scarring in the liver or other organs.

Both kinds of receptors are found in the skin.
- Exciting therapeutically due to accessibility (don't need to go through a lot of layers to be active)
- Currently an area of intense research.

CBD, which doesn't attach to either receptor with any real affinity seems to be a valuable cannabinoid for the skin.
- A full-spectrum cannabis extract with CBD would show antibacterial effects (as in acne).
- CBD works on TRPV-4 receptors, which reduces the release of fat (sebum), which contribute to acne. seÂ·bum
ˈsēbəm/
noun
an oily secretion of the sebaceous glands.

Sebum Definition - Verywell
Apr 15, 2017 - Sebum is a light yellow, oily substance that is secreted by the sebaceous glands that help keep the skin and hair moisturized. Sebum is made up of triglycerides, free fatty acids, wax esters, squalene, cholesterol esters, and cholesterol. ... It also includes lipids from skin cells, sweat, and environmental matter

CBD was recently shown to stimulate bone fracture healing.
- Right now cannabinoids are banned from professional and amateur sports. It might be time to rethink that. Cannabidiol will speed the healing, without side effects.

Cannabis will accelerate the heart rate.
- Interestingly, at a higher dose it will slow the heart rate down, far enough to make it difficult to regulate blood pressure.
- You can pass out from orthostatic hypertension.

Concerns:
- There was a rise in concern that cannabis might contribute to heart attack, but the thinking is the signalling isn't strong enough to make this drastic an effect. It may be a concern for individual patients, but not as a population concern.

- For a time there was concern that there might be an arthritic response to cannabis. Upon closer inspection it was discovered that the patients were all tobacco smokers, and tobacco is known to constrict blood vessels in the hands (Berger's Disease).

The most common use of cannabis is for the treatment of chronic pain conditions. Cannabis offers relief through various pathways
- Through neurotransmitters
- through interaction with opioids, whether by pill form or the endogenous opioid system
- direct effects in the brain
- other components in cannabis beyond the major cannabinoids, CBD and THC

The brain has a base-line level of cannabinoid function (the endocannabinoid tone)
- Under certain conditions activity can be either depressed or enhanced.
- the periaqueductal gray is a mind brain generator (???)

The periaqueductal gray, or PAG, is an area of gray matter found in the midbrain. The PAG surrounds the cerebral aqueduct (hence the name periaqueductal) and occupies a column of brainstem that stretches about 14 mm long. There are no obvious visible anatomical divisions within the PAG, but researchers have divided the PAG into four columns based on differences in connectivity and function: the dorsomedial, dorsolateral, lateral, and ventrolateral columns.

What is the periaqueductal gray and what does it do?

Although the functions of the PAG are complex and not fully understood, since the 1970s it has best been known for its role in the inhibition of pain. Indeed, some have argued that its identification as an "analgesia center" has hindered a more complete understanding of the functions of the PAG. An increasingly intricate appreciation of PAG function, however, has been emerging over the past few decades

When the PAG was first found to have an association with pain, it was observed as playing a role in pain transmission---or the sending of pain signals to the cortex---and not the mitigation of those signals. Eventually, the PAG would come to be much better recognized as an area important to pain inhibition. In the late 1960s, the first indication of the role of the PAG in pain suppression emerged from a study that found that stimulation of the PAG in rats allowed researchers to perform surgery on the rats without the use of anesthetics (and without the animals exhibiting signs of severe pain). Further studies found that PAG activation was associated with the inhibition of spinal cord neurons involved in pain signaling. By the mid-1970s, stimulation of the PAG was already being used as an experimental approach to treating chronic pain in human patients. The fact that some of these experiments reported success in the treatment of chronic pain supported the role of the PAG in analgesia. The patients involved in these experiments also often complained of a wide range of side effects linked to PAG stimulation, however, suggesting that many more functions than analgesia were connected to the PAG.

- Cannabinoids also active in the thalamus (ventral postural lateral nucleus). Tested in this area cannabinoids are 10 times more powerful than morphine. It becomes obvious that using the two drugs together would be a beneficial approach for pain management.

- There are additional functions in the spinal cord by which cannabinoids effect pain levels and perception.

Cannabinoids can be effective against contact dermatitis (poison ivy or plain old itching)

There are numerous randomized trials on cannabis and pain. The problem is that the company that holds the rights to market isn't choosing to do so in many markets. Just exactly what we anticipated. Give Big Pharma control and they won't market something they can't make the big money on. Keep this plant out of their hands and in the control of the people.

An interesting thing occurred when they tested cannabis with cancer pain in hospice settings. The patients got relief and the tolerance levels didn't rise in the same way they see with opioids. There wasn't the standard increase in pain levels with cannabis or Sativex.
- The gold standard in pain is the group that has a 30% reduction in pain over time.
- In the study 43% of patients using Sativex got relief, as opposed to 21% with the placebo.
- The study contrasted placebo, Sativex and a full THC isolate extraction. The isolate didn't work any better than the placebo. The Sativex, with its inclusion of CBD, did work, and in dramatic fashion.
- This was the first concrete evidence of th entourage effect in pain control.

Placebos work Faith is a powerful tool, and I'm convinced the ECS can heal a disease-wracked body instantaneously, so the placebo effect doesn't surprise me in the slightest.
- Have a placebo that works so well and you'll end up with your effective drug looking ineffective next to the placebo, making your drug look statistically insignificant.

In a randomized withdrawal study of Nabixinol,Sativex, and MS patients were unknowingly started on Sativex at either a level to control spacisity or to keep them from having too many side effects.
- The 20% who improved were brought back and then randomly half were refilled with placebos.
- All patients who stayed on Sativex improved spacisity, and all patients on the placebo went into decline.
- These results were the impetus for gaining approval for Sativex administration in 27 countries. Are we one of those lucky countries?
- They had patients with twisted limbs that had the muscles relax after administration of Sativex I believe Sayivex is a balanced ratio medication.

Clinical Endocannabinoid Deficiency
- Your endocannabinoid tone is an indicator of the number of cannabinoids available, how their produced and degraded, and how many receptors you have available.
- A change to any of those areas can effect the endocannabinoid tone, resulting in pain, stiffness in the muscles, the seizure threshold, etc.
- The theory was that in certain conditions if the tone is depressed too low it'll produce disease and symptoms in the system.
- In original 2004 paper he focused on migraine, fibromyalgia and IBS. All three are hyper analgesic responses, where the system has a heightened pain response.
- All three are difficult, if not impossible to track or determine by lab testing, so they're diagnosed based on clinical determination of the patient's described patterns.
- They're all also comorbid, meaning if you have one, you likely have the other two. Primary headache turned up in 97% of the cases with fibromyalgia. 33% of patients with chronic daily headaches (a type of migraine) also had fibromyalgia. 32% of patients with IBS had fibromyalgia and 32% of fibromyalgia patients also had IBS.

Unfortunately, these conditions show up in large numbers of women who get misdiagnosed as being psychosomatic by their male doctors.
- Russo maintains that this is a biochemical disorder, possibly due to a drop in endocannabinoid expression, and there's no mind game these women are playing with themselves.

IBS: Sometimes thought of as a life-long condition, but people clearly acquire this at some point.
- It's the most frequent diagnosis among gastroenterologist in the states.
- There are no particular regular signs, but there is a pattern of irregular bowel movements, often diarrhea, although this could be constipation. They can alternate too.
- It's being described as a disorder of unknown origin and treated by agents of an unknown mechanism of action.
- There are many ineffective drugs. The target should be the ECS instead.
- IBS brings the joy of visceral hypersensitivity. Things hurt, and hurt bad. Again, an over abundance of pain.
- It's known that anandamide works with colonergic neurons, the primary movers of the gut. It performs a modulatory role on the speed of digestion and elimination.
- The ECS appears to be unregulated in diseases of the gut with inflammation. This would be true in the case of IBS as well.

The Mayo clinic, looking at genetic markers of IBS, found CNRI (has to do with cannabinoid function)
- Patients with IBS responded positively to THC.
- CB1 receptors seem to modify the speed through the gut.

Relationships to diet
- If you eat the right things you might not have to use cannabis so much.
- Replenishing the gut flora with probiotics enhanced pain management. They positively effect the RNA expression of the gene associated with CB receptors when taken as a supplement.
- This enhanced the pain control function of morphine.
- It was proposed that taking a CB2 antagonist would enhance that function.
- 32 out of 45 studies on the addition of probiotics showed an improvement in gut performance and health for patients with IBS, incl. less pain, less bloating, etc...
- 5-6 months of continuious supplementation created a stable environment in the gut.

A recent study found that THC alters the bacterial presence in the gut.
- In these mice that had a predisposition to being obese, the THC prevented weight gain through the action of changing the balance of the gut bacteria.

Prebiotics, vegetable matter that feed the good gut flora. (FOS) They don't get broken down in the stomach and they're fermented by the gut flora.
- There are over a thousand different species of bacteria being brewed.
- Prebiotocs help the healthy, beneficial gut flora grow and prosper.
- It's estimated that ancient man ate a lot more of these valuable vegetables. Modern humans may only get a few grams a day.
- Best sources acacia fiber, gum arabic, chicory, burdock, sunchokes (Jerusalem artichoke), onions, leek, garlic, dandelion greens,
- They reduce infectious diarrhea, alleviate inflammatory bowel diseases, reduce cancer risk in the gut, increase mineral absorbtion, lower cardiac risk, and decrease obesity.
- 10 grams a day - a heaping tablespoon of acacia fiber that could be added to any number of foods, increased lactobacillus sixfold and increased balance of the gut flora. It also appears to decrease the bug that causes c-diff.

All of this information on the gut is in a recently published article (published last May or June).

Fibromyalgia
- German study looked at nine patients of fibromyalgia, taking up to 15 mg of THC daily.
- It was a THC isolate, and too strong an experience for 5 of the 9, who dropped out of the study.
- The remaining 4 patients saw relief, a decrease in Allodynia (extremely painful touch), or Hyperalgesia (hyper sensitivity to pain).
- Also saw a sipratistically significant reduction in pain overall. Statistically, this should only happen in 1 out of 100 patients, and yet all four saw this improvement.

Nabilone is a THC semi-synthetic marketed in some countries.
- It's about 10x the potency of THC. Not really therapeutically useful except in the most extreme cases, and even then.....
- Study tracked 40 patients that got one dose a day equivalent to 20 mg of THC, a fairly high dose.
- After four weeks a review of a visual analog scale (where patient judges their pain on a numeric scale), the Fibromyalgia Impact Questionaire, and anxiety levels.
- Improvement was statistically significant across the board.
- Regardless, not a drug that patients can take over the long run with any success.

Mark Ware in Canadian study contrasted Nabilone compared to Amotriptoline (?), a commonly prescribe bed drug for fibromyalgia, looking at sleep.
- 100% of fibromyalgia patients suffer from sleep disturbance. Patients won't improve until sleep is restored.
- In this study sleep was improved, but there was no significant reduction in pain.

A Spanish study of smoked cannabis was only done acutely, looking at pain, stiffness, relaxation, sleepiness, and wellbeing.
- 28 patients with cannabis, 28 controls.
- Within 2 hours, many parameters were statistically improved.
- Mental health component was also higher in the group that recieved cannabis, meaning they had psychoactive side effects.
- It's almost a given that it was a high THC variety used in this study, with no Cannabidiol because that was what was available at the time of the study.

National Pain Report looked at 1300 patients with fibromyalgia and asked for their benefits from taking 3 FDA-approved drugs commonly prescribed for fibromyalgia, contrasted with cannabis.
- The Pharma drugs were basically ineffective.
- Over 60% of cannabis-using patients claimed a really good result and found cannabis effective. Only 5% had no benefit with cannabis.
- Which is the best choice? Hands down cannabis.

Migraine
- For a common affliction migraine is probably the most biochemically complex malady people suffer.

Study of women with migraine looked at the anandamide membrane transporter and the activity of FAAH (enzyme that degrades anandamide).
- Looking at platelets in the blood (brain tissue isn't ethical in living patients :3.
- Compared patients with chronic headaches vs controls.
- Levels of CB1 receptors were equivalent in the two groups, but women with migraine had an increased degradation rate of anandamide, and decreased platelet levels that could indicate an ECS deficiency that was contributing to the migraine.

Airman et al did a series of studies looking at ECS function in migraine.
- One of the things that migraine does is make blood vessels too big or too small. Not the cause of the disease, just an epiphenomonen, a secondary effect.
- Anandamide reduced blood vessel diameter in the dura ( the protective cover of the brain) by 30%, through a complex biochemical mechanism.
- It was felt that anandamide maintains a base level in the brain (a tonic level of activity).
- Anandamide modifies the trigeminalvascular system, the path of physiological mechanism in migraines.

Another study of the vascular system showed the involvement of TRRP-V1 set of eCB receptors.
- Used a synthetic cannabinoid, looking at synaptic activity.
- Study suggested that CB1 antagonists like THC have therapeutic promise in migraine and cluster headaches.
- Authors were fearful of the psychoactive side effects.
- Overlooks the fact that a very low dose, that isn't psychoactive is sufficient to treat these disorders, or that you can temper the euphoria with the inclusion of Cannabidiol or terpenoids.

Probable the best evidence of clinical eCB deficiency is a study proposed in 2004 but carried out later by the Italians.
- He suggested that looking at cerebral spinal fluid for levels of eCB in patients with migraines.
- It requires a spinal tap, something the ethics committees in the US would be adverse to allow.
- The Italian researchers looked at normal levels (it's unknown how they convinced the patients to do a spinal tap - maybe ethics weren't the big concern in Italy) in control group, contrasted by patients with migraines.
- Only a 1 in 10,000 possibility that the results were by chance.
- Author said "Reduced eCB levels in the cerebral spinal fluid of chronic migraine sufferers support the hypothesis of the failure of the ECS in chronic migraine.
- This proves the existence of clinical eCB deficiency.

In another Italian study, both anandamide and 2-AG markers were dramatically reduced in the platelets of chronic migraine patients as compared to controls.
- Very highly statistically significant.

In another Italian study an animal model of migraine is explored.
-Migraine creates some bizarre symptoms, like the loss of vision on one side with bursts of light (sparkles), caused by a depression on the surface of the brain.
- The study showed the involvement of the ECS. Theoretically, THC could prevent or stop the progression of this effect.
- Many patients report that cannabis is used at the onset of the array it will prevent the symptom from becoming full-blown.

There's a genetic predisposition to migraine.
- It's been mapped to CNR1, an eCB gene, on chromosome 6.
- Patients with the strongest evidence for this gene also had the highest likelihood of having symptoms like sensitivity to light, nausea, and significant disability with their headaches.
- Patients with strongest evidence of CNR1 also showed neuroticism, depression, and a tendency towards drug dependence. (Someone with mirgraines will obviously be trying to treat it with one substance or another.)

Study out of Colorado in mid 2016 looked at 120 patients with migraine using cannabis to prevent or control migraine.
- Patients were treated prophylactically to prevent migraine.
- 60% of patients had used cannabis previously.
- Of those who went on to use cannabis regularly dropped the occurance rate from 10.4 a month to 4.6 a month, very statistically significant.
- Also reduced headache frequency and were able to abort, or stop their headaches when cannabis was used acutely.
- It's a selective population. The same thing needs to be done in randomized, controlled trials. Russo has been unsuccessfully trying to get those trials to happen for over 20 years.

Where do we go from here?
- We need better studies of IBS, Fibromyalgia, and migraine, looking for levels in the blood, levels in the cerebral spinal fluid.
- It'd be better to do this with scans of the brain, but for right now we don't have great tools this way.
- There's active research, but it'd be nice to be able to assess the eCB function or eCB density in the brain without having a needle stuck into your back.
- We need better work genetically. There are companies looking for markers of these diseases and trying to coordinate them with eCB function.
- Controlled clinical trials of cannabis-based medicines in these clinical conditions are what will convince physicians and politicians.

"Only time and the scientific method will ascertain whether a new paradigm is applicable to human physiology and the treatment of its derangements. Our insight into these possibilities is dependent on the contribution of one unique healing plant. For clinical cannabis has become a therapeutic compass to what modern medicine fails to cure."

Cannabis modulates the ECS, which is, in itself, an innate homeostatic regulator of human physiology. If there's too much of something, it brings it back down into balance. It there's too little of something, it brings it up into balance.
- Cannabidiol is a particularly interesting cannabinoid system modulator.
- In future we may see more CBD with only a little THC.
- The ECS is influenced by lifestyle and dietary factors.
- Primary beneficial approaches would be low-impact exercises, an antioxidant, anti-inflammatory diet, probiotics and probiotics. Of of these will improve the conditions discussed.

Negative emotion is nothing more than levels of judgement you choose to express. Those expressions help to define your reality. Is that the reality you want? I'd prefer a reality fueled by my proclivity to be joyful and avoid judgement of myself or anyone else.

A reality where I'm satisfied not to read between the lines.

You feel negative emotion because you chose to leave joy mode and tumble down the vibrational ladder. The further you allow yourself to fall the more intense the level of judgement and the more tension you build internally. You're looking at the situation in a way contrary to the creator, however you define that being.

Remember you're evolved to heal, to maintain a level of homeostasis that keeps you running smoothly through the continuious action of creation. I find that thought incredibly inspiring. At any given moment there's creation going on all through your body with the express purpose to modify cellular signalling and keep the community of individual cells healthy and strong.

We are actively creating all the time. If we choose a vibration with negative tones the consequences may include disease. Create enough tension in the body and cellular signalling is compromised. Homeostasis becomes a memory.

The thought is that choosing to go anywhere other than joy creates tension, chiefly because you're ignoring the impulse of the creator to love unconditionally. You cause a disruption in the communication between you and the cosmic forces that work tirelessly on your behalf.

In so doing you create a communications nightmare for the cells that make up you. Because "you" run best in joy mode, when energy flows freely and cellular signalling is clear, allowing for timely response to any cell out of vibration with "healthy and whole."

Learned this one in the 70's, a gift from my grandpa.

I see myself as God sees me, strong, healthy, and wise, with plenty to fill my every need.

As I learn more about the marvelous ECS I'm coming into a deeper understanding of what this affirmation means.

New studies have uncovered the fact that different ligands can activate different G-protein receptors and change their shape, and thereby their activity. What it means is the system is much more dynamic than anyone imagined.

This is really exciting news!

I want to know what the ECS is listening for and how it senses that message. I suspect it's vibration, that each cell has a vibratory tone and the body, in the state of homeostasis, has a particular community tone. When a cell is struggling it emits a different vibratory tone, and somehow the body recognizes that variation from the community norm and responds by creating a particular cannabinoid that emits a particular signal to that cell. The resulting chemical cascades generate the cellular response designed to bring that ailing cell back into a healthier vibration.

Let's see how long it takes the lab rats in the real world to prove my theory correct.

Excerpt from "Super Brain Solutions." It was a random book I found on a shelf at the library, and neglected to take note of the author. The thoughts are from the chapter on Self Healing.

Being your own placebo is the same as freeing up the healing system through messages from the brain. All healing is, in the end, self-healing. Physicans aid the body's intricate healing system (which coordinates immune cells, inflammation, hormones, genes, and much else), but actual healing takes place in an unknown way.

When it comes to the mind-body connection, healing should involve the following basic conditions:

* The mind is contributing to getting well.
* The mind doesn't contribute to getting sick.
* The body is in constant communication with the mind.
* This communication benefits both the physical and mental aspects of being well.
* Once a person receives treatment that he trusts, he lets go and allows the healing response to proceed naturally

When the placebo effect works, all five aspects are involved. The patient's mind cooperates with the treatment and trusts it. The body's aware of this trust. There is open communication, and as a result, cells theouout the body participate in the healing response. The healing system as a whole is incredibly complex and all but impossible to explain as a whole. We only know how parts of it operate, such as antibodies and the immune response to infection.

How can we bring about these five conditions consciously? At the very least we shouldn't be fighting them with fear, doubt, skepticism, hopelessness, and despair. Those states convey their own chemical messages to the body. When you believe that a sugar pill is going to cure you, those healing messages will begin to have an effect. But we cannot say that the 30 percent who benefit from the placebo effect are doing something right when the remaining 70 percent aren't. Everyone's medical history is different; the healing system remains too murky to be accurately measured. Deep negative feelings, if they are blocking the placebo effect (by no means a certainty), are complex and frequently unconscious, so the difference here isn't simple.

The greatest promise lies in the fact that a mental intention of "I shall please" is known to work. Being your own placebo requires applying the same conditions as in a classic placebo response:
1. You trust what is happening.
2. You deal with doubt and fear.
3. You don't send conflicting messages that get tangled with each other.
4. You have opened the channels of mind-body communication.
5. You let go of intention, and let the healing system do its work.

When a symptom is minor, such as a cut finger or a bruise, everyone finds it easy to let go and stop interfering The mind doesn't intrude with doubts and fears. But in serious illness doubts and fears play a marked role, which is why a practice like meditation or going......

........The very important task of being aware of your body doesn't have to be boring. You most need mind and body to become friends again, to go back to their natural alliance. One way to do so is to sit quietly with your eyes closed and simply feel the body.

Let any sensation come to the surface. Don't react to the sensation, whether pleasant or unpleasant. Just relax and be aware of it. Notice where the sensation is coming from. You won't have only one sensation or feeling. You will find that your awareness goes from place to place, one moment noticing your foot or your stomach, your chest or your neck. This simple exercise is a mind-body reconnection. Too many people are in the habit of paying attention to only the most gross signals from their bodies, such as acute pain, stiffness, or nausea, and other hard-to-ignore discomforts. What you want to do is increase your sensitivity and your trust at the same time. Your body knows at a subtle level where dis-ease and discomfort are. It sends signals at every moment, and such signals are not to be feared.

Even if you consciously ignore what is happening in your cells, just below your awareness, unconscious information is being exchanged. When the federal government recently decided that annual mammograms were no longer necessary for younger women, one consideration was that 22 percent of small breast tumors resolved themselves, disappearing spontaneously. So an automatic reaction of fear, even in the face of possible cancer, is unrealistic at the level of the healing system. Your immune system eliminates thousands of abnormal cells everyday. Everyone has tumor-suppressing genes, although how they can be triggered is as yet unknown.

The best future of self-healing will unfold from the proven fact that every cell in the body knows, through chemical messengers, what every other cell is doing. Bringing your conscious mind into the loop adds to this communication. Advanced yogis can alter their involuntary responses at will, such as lowering their heart rate and breathing to very low levels or increasing skin temperature in a very precise way. You and I have the same abilities, although we don't consciously use them. You can follow an exercise to make a spot on your hand grow warmer, and it will happen, even though you never used that ability before.

We can venture that the placebo effect falls into the same category. It's a voluntary response that we could use, if only we learned how to. The healing system seems to be involuntary. You don't have to think in order to heal a cut or a bruise. But the fact that some patients can make their own pain go away when given a sugar pill implies, very strongly, that intention makes a difference in healing. We aren't talking about positive thinking, which is often too superficial and masks underlying negativity. Instead we are encouraging a lifestyle that bonds a deeper mind-body connection.

The movement of the proteins is the job of the cannabinoids, among other components. They belong to the group Bruce refers to as "signals". When the cannabinoids attach and pass their signal they cause the gene to move.

UNDERSTANDING!!!

Back to the show.

21:30 "The brain of the cell is the structure that tells the cell what to do in response to the environment."

The brain of the cell is the skin of the cell. The human brain is derived from the skin.

The nucleus of the cell is really the gonad, the reproductive organ. If I need a part, it's the nucleus that has the patterns to construct all the different things the body needs to function. It's the repository for the patterns for all the parts needed for the human body. The nucleus holds the blueprints. There's no intelligence going on, just function.

There are no brains involved with genes. Genes are not capable of that. They function mechanically, stimulated by the signals.

The membrane picks up the primary signal, the environmental signal. The environmental (Primary) signal is converted into a signal that controls the protein (Secondary signal).

Behavior is mediated by the cell membrane as it responds to the environment.

If you cut off the environment the cell has no behavior. It has no life. Life is due to the response to the environment. Your life is how you respond to your environment. You percieve the environment and take action based on your perceptions.

At about the 30 minute mark there begins an excellent explaination of cellular signalling that drives cellular behavior. "

Change is a combining of input and output. Ex: a receptor picks up a signal, and it causes a change in the shape of the receptor's gene that now is a perfect fit for the connector for a channel, allowing the channel to open.

Quitting at 31:16. Time to rest the eyes. Time for bed.

Goodnight moon.

Couldn't stop yet.

There's a freeze in the coverage for over half an hour. :17: You gotta wonder what's on there.

The behavior of the cell isn't programmed. The behavior of the cell is in response to the perception of the environment.

When presented with an environmental signal the cell has to decide whether to respond in growth or reproduction. Cells move towards positive signals for growth. They move away from negative signals for protection. Fella's can't move IB both directions at the same time.

"The most growth-promoting signal in the world today, if you're a human, is love." - Dr. Bruce Lipton

Love exceeds nutrition in growth potential. A malnourished child getting love will continue to grow. Children provided nutrition but deprived of love will have their growth stunted in every imaginable way.

The Hypothalamus Pituitary Adrenal Axis is crucial to this discussion. It's the hypothalamus that intreperts the environmental signals and makes the determination of growth or protection. If it's a negative signal (stress) it activates the pituitary gland, the master gland, that controls the shape of the body. There are two shapes, growth or protection.

Stress activates fight or flight. The viscera houses the organs. It's growth. The muscles are for protection. Stress causes hormones from the adrenal gland which construct blood flow to the viscera and push it to the muscles for protection mode.

Under stress you shut down your growth mechanism.

The adrenal system is to protect you from percieved dangers in the environment. The immune system is to protect you from invasions to the system. When the adrenal hormones get to a certain level it shuts down the immune system. Stress shuts down both growth and internal protection.

When you're under stress you're opening yourself up to illness.

The hormones that construct blood flow to the viscera and push that blood flow to the muscles also restrict blood flow to the frontal lobe and send it to the back of the brain that directs reflex behavior. Under stress you are less intelligent.

The cell percieved the environment and creates a complimentary copy of that in the nucleus. The cell will make a physical structure to compliment the environment. Perception is belief. Belief is simply a thought you keep thinking, and the wonderful news is that we can change the belief, and in so doing chance get our perception, and thereby our cellular responses and behavior. Living in stress/fear makes you reactionary, prone to sickness, stunted in growth, and less intelligent.

You get to choose how you percieve the environment. No one else has the power to do that for you. You have the power to change how you see the environment you're living in.

Belief filters aren't helpful if they're inaccurate to reality. If your perceptions are off you're going to choose genes that are inappropriate to the environment. The filters are learned, some passed on before we were born.

How I see it effects who I am. The perception interfaces with the environment and your biology, but your perception is belief. Beliefs act as a filter between your biology and the environment.

Life has everything, but you'll only pick up what your belief filters allow you to see. You were taught those perception/belief filters. Your mother started influencing you in the womb. Your parents program you from birth. Schools, churches, clubs, etc, etc.

You can selectively choose healthier, growth-satisfying filters and incorporate them fairly rapidly, with deliberate intention. You get to decide which genes will be expressed and those expressions drive your personality, and by default, your actions.

Well-Known Member

Sue.... your breakdown of this was amazing, wanted to say hello
Thank you

QUOTE=SweetSue;3693781]

18:15 seconds in:

"What is life? Life is the movement of the proteins."

I know this! I know this!

The movement of the proteins is the job of the cannabinoids, among other components. They belong to the group Bruce refers to as "signals". When the cannabinoids attach and pass their signal they cause the gene to move.

UNDERSTANDING!!!

Back to the show.

21:30 "The brain of the cell is the structure that tells the cell what to do in response to the environment."

The brain of the cell is the skin of the cell. The human brain is derived from the skin.

The nucleus of the cell is really the gonad, the reproductive organ. If I need a part, it's the nucleus that has the patterns to construct all the different things the body needs to function. It's the repository for the patterns for all the parts needed for the human body. The nucleus holds the blueprints. There's no intelligence going on, just function.

There are no brains involved with genes. Genes are not capable of that. They function mechanically, stimulated by the signals.

The membrane picks up the primary signal, the environmental signal. The environmental (Primary) signal is converted into a signal that controls the protein (Secondary signal).

Behavior is mediated by the cell membrane as it responds to the environment.

If you cut off the environment the cell has no behavior. It has no life. Life is due to the response to the environment. Your life is how you respond to your environment. You percieve the environment and take action based on your perceptions.

At about the 30 minute mark there begins an excellent explaination of cellular signalling that drives cellular behavior. "

Change is a combining of input and output. Ex: a receptor picks up a signal, and it causes a change in the shape of the receptor's gene that now is a perfect fit for the connector for a channel, allowing the channel to open.

Quitting at 31:16. Time to rest the eyes. Time for bed.

Goodnight moon.

Couldn't stop yet.

There's a freeze in the coverage for over half an hour. :17: You gotta wonder what's on there.

The behavior of the cell isn't programmed. The behavior of the cell is in response to the perception of the environment.

When presented with an environmental signal the cell has to decide whether to respond in growth or reproduction. Cells move towards positive signals for growth. They move away from negative signals for protection. Fella's can't move IB both directions at the same time.

"The most growth-promoting signal in the world today, if you're a human, is love." - Dr. Bruce Lipton

Love exceeds nutrition in growth potential. A malnourished child getting love will continue to grow. Children provided nutrition but deprived of love will have their growth stunted in every imaginable way.

The Hypothalamus Pituitary Adrenal Axis is crucial to this discussion. It's the hypothalamus that intreperts the environmental signals and makes the determination of growth or protection. If it's a negative signal (stress) it activates the pituitary gland, the master gland, that controls the shape of the body. There are two shapes, growth or protection.

Stress activates fight or flight. The viscera houses the organs. It's growth. The muscles are for protection. Stress causes hormones from the adrenal gland which construct blood flow to the viscera and push it to the muscles for protection mode.

Under stress you shut down your growth mechanism.

The adrenal system is to protect you from percieved dangers in the environment. The immune system is to protect you from invasions to the system. When the adrenal hormones get to a certain level it shuts down the immune system. Stress shuts down both growth and internal protection.

When you're under stress you're opening yourself up to illness.

The hormones that construct blood flow to the viscera and push that blood flow to the muscles also restrict blood flow to the frontal lobe and send it to the back of the brain that directs reflex behavior. Under stress you are less intelligent.

The cell percieved the environment and creates a complimentary copy of that in the nucleus. The cell will make a physical structure to compliment the environment. Perception is belief. Belief is simply a thought you keep thinking, and the wonderful news is that we can change the belief, and in so doing chance get our perception, and thereby our cellular responses and behavior. Living in stress/fear makes you reactionary, prone to sickness, stunted in growth, and less intelligent.

You get to choose how you percieve the environment. No one else has the power to do that for you. You have the power to change how you see the environment you're living in.

Belief filters aren't helpful if they're inaccurate to reality. If your perceptions are off you're going to choose genes that are inappropriate to the environment. The filters are learned, some passed on before we were born.

How I see it effects who I am. The perception interfaces with the environment and your biology, but your perception is belief. Beliefs act as a filter between your biology and the environment.

Life has everything, but you'll only pick up what your belief filters allow you to see. You were taught those perception/belief filters. Your mother started influencing you in the womb. Your parents program you from birth. Schools, churches, clubs, etc, etc.

You can selectively choose healthier, growth-satisfying filters and incorporate them fairly rapidly, with deliberate intention. You get to decide which genes will be expressed and those expressions drive your personality, and by default, your actions.

Abstract
A great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (that is, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics. Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models. Emerging clinical studies show that 'medicinal' cannabis or cannabinoid-based medications relieve pain in human diseases such as cancer, multiple sclerosis, and fibromyalgia. However, clinical data have yet to demonstrate the analgesic efficacy of inhibitors of endocannabinoid-regulating enzymes. Likewise, the question of whether pharmacotherapies aimed at the endocannabinoid system promote opioid-sparing effects in the treatment of pain reflects an important area of research. Here we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.

The ECS creates homeostasis by balancing the CNS and the immune system, which is most prevalent in the periphery.
- The CNS controls pain signaling and........still piecing all this together. I'm pretty sure the CNS is major organs. Hmmm..... what about the gut? It's from one end of the system to the other and has its own brain. More thought for later.
- The immune system manages inflammatory response and invasions.

Those are rudimentary ways of thinking of the CNS and immune system, but for my purposes it works. As with all of this, it's a work in progress.

My theory:

Each cell vibrates, and when it's healthy it vibrates a particular homeostatic tone.

Because in this vibratory universe like attracts like, the neighboring cells share this homeostatic tone.

When a cell becomes diseased or damaged it changes the emitted tone, which causes a ripple effect through the cellular community.
- This may be what alerts the ECS. It's just as likely in my mind that the ECS responds almost immediately right there on the spot, as soon as the vibration changes. Our self-imposed tensions block the signals somehow.

It has always struck me as significant that cancer cells express a higher concentration of eCB receptors, as though they're asking for cannabinoids to help them keep from continuing down the path of distruction of the community. It's the nature of the cells to work for the greater good. I don't think cancer cells want to continue proliferating. I think they want the ECS to stop them.

It occurs to me that we think of the cannabinoids as creating angiogenesis by cutting off the blood supply to cancerous cells. Could it be that what really happens is they create a vibration that allows the cancer cells to turn off this behavior of creating compensatory blood vessels?

We think of the cancer cells as something evil. Maybe that's not the case at all. Maybe they know they're off-kilter and they go out of their way to alert the system that they're there, at least until they mutate far enough to begun stealth practices. Even cells have psychotics, apparently.

So if the ECS is active in controlling cancer proliferation, why do they keep proliferating? Because we shortchanged the body in raw materials and created unbelievable stressers in our societies, which created Endocannabinoid system deficiencies leading to disease. Eliminate cannabis while introducing pharmaceuticals and you have a perfect storm.

You also have a powerful healing force, which I believe is capable of working with next to nothing and still continue to signal spontaneous healing.

We call it an ECS. Everyone has one. It's healing you all the time. If it didn't you'd be dead. Lol!

Enough of my diversions. Back to my stoner ramblings.

The cannabinoids that respond and stimulate the receptors change the vibration of the cell to something that benefits the community at large.
- Sometimes this is the cell disassembling with ceramide-induced apoptosis.
- Sometimes it's a vibration that causes other chemical cascades, but there's always a change in the vibration.
- Neurochemicals either excite or calm the system at large.

joy is the vibration most conducive to healing. It's your individual homeostatic tone. When you've learned to create joy, real joy, on demand, you can feel the vibration change, and it feels something like a cascade sometimes. Lol! Hadn't thought of that.

My gut feeling is that our bodies run most efficiently when we can think of life in playful, wonderous terms. When we're joyful we're closest to fine-tuned, and the further we move from joy the more tension we create system-wide, and it becomes easier to get sick. Then there's an increased possibility that your illness will begin to direct your thoughts. Yikes!

Your thoughts create your chemical dumps, which guide your feelings, which determine your personality expression and your interpretation of the world around you, including your level of perception of threat, what you fear. The healthier the ECS the less you fear.
- Joyful, loving, grateful thoughts support healing.
- Fearful, angry, frustrated thoughts promote sickness.

Anyone can systematically train to a default to joy. There are any number of proven, simple ways to accomplish this. Some will resist the process longer, but when you're ready to give up sickness you tend to find a way and excuses peter out.

But how would you research something like this? What are you looking for? What are we measuring? And if it turns out be a valid theory that your thoughts create your reality by influencing the ECS, how do you make sense of that and explain it to people in a way they can understand and accept? Something more than "do it because it works."

Most of the time when discussing this concept of your thoughts creating the biological expression of you, I hear "I do my best to think positive thoughts." This is not positive thinking. This is deliberate thinking, and how do you measure the effects? What baseline do you establish, and how do you track change in ECS response?

Hmmm.....If I were going to write a grant proposal what would it be for?

A lot of questions I don't need to be the one to answer. Lol! I'll grab the satisfied feeling of figuring the mysteries out, one-by-one, and having fun doing it. Then watch where the universe takes me.

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